Method and system for setting cardiac resynchronization therapy parameters

ABSTRACT

A method or system for computing and/or setting optimal cardiac resynchronization pacing parameters as derived from intrinsic conduction data is presented. The intrinsic conduction data includes intrinsic atrio-ventricular and interventricular delay intervals which may be collected via the sensing channels of an implantable cardiac device. Among the parameters which may be optimized in this manner are an atrio-ventricular delay interval and a biventricular offset interval. In one of its aspects, the invention provides for computing optimum pacing parameters for patients having some degree of AV block or with atrial conduction deficits. Another aspect of the invention relates to a pacing mode and configuration for providing cardiac resynchronization therapy to patients with a right ventricular conduction disorder.

FIELD OF THE INVENTION

This invention pertains to methods and apparatus for treating cardiacdisease with electrical therapy.

BACKGROUND

Cardiac rhythm management devices are implantable devices that provideelectrical stimulation to selected chambers of the heart in order totreat disorders of cardiac rhythm. A pacemaker, for example, is acardiac rhythm management device that paces the heart with timed pacingpulses. The most common condition for which pacemakers are used is inthe treatment of bradycardia, where the ventricular rate is too slow.Atrio-ventricular conduction defects (i.e., AV block) that are permanentor intermittent and sick sinus syndrome represent the most common causesof bradycardia for which permanent pacing may be indicated. Iffunctioning properly, the pacemaker makes up for the heart's inabilityto pace itself at an appropriate rhythm in order to meet metabolicdemand by enforcing a minimum heart rate and/or artificially restoringAV conduction.

Pacing therapy can also be used in the treatment of heart failure, whichrefers to a clinical syndrome in which an abnormality of cardiacfunction causes a below normal cardiac output that can fall below alevel adequate to meet the metabolic demand of peripheral tissues. Whenuncompensated, it usually presents as congestive heart failure due tothe accompanying venous and pulmonary congestion. Heart failure can bedue to a variety of etiologies with ischemic heart disease being themost common. It has been shown that some heart failure patients sufferfrom intraventricular and/or interventricular conduction defects (e.g.,bundle branch blocks) such that their cardiac outputs can be increasedby improving the synchronization of ventricular contractions withelectrical stimulation. In order to treat these problems, implantablecardiac devices have been developed that provide appropriately timedelectrical stimulation to one or more heart chambers in an attempt toimprove the coordination of atrial and/or ventricular contractions,termed cardiac resynchronization therapy (CRT). Ventricularresynchronization is useful in treating heart failure because, althoughnot directly inotropic, resynchronization can result in a morecoordinated contraction of the ventricles with improved pumpingefficiency and increased cardiac output. Currently, a most common formof CRT applies stimulation pulses to both ventricles, eithersimultaneously or separated by a specified biventricular offsetinterval, and after a specified atrio-ventricular delay interval withrespect to the detection of an intrinsic atrial contraction and/or anatrial pace. Appropriate specification of these pacing parameters isnecessary in order to achieve optimum improvement in cardiac function,and it is this problem with which the present invention is primarilyconcerned.

SUMMARY

The present invention relates to a method or system for computing and/orsetting optimal cardiac resynchronization pacing parameters as derivedfrom intrinsic conduction data. Such intrinsic conduction data may becollected via the sensing channels of an implantable cardiac device andeither utilized by the implantable device itself to compute optimalpacing parameters or transmitted to an external programmer via awireless telemetry link. In one of its aspects, the invention providesfor computing optimum pacing parameters for patients having some degreeof AV block or with atrial conduction deficits. Another aspect of theinvention relates to a pacing mode and configuration for providingcardiac resynchronization therapy to patients with a right ventricularconduction disorder.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system diagram of exemplary hardware components fordelivering cardiac resynchronization therapy.

FIG. 2 is a timing diagram showing the relationship between the RA-LAinterval and the programmed AVD interval.

FIG. 3 illustrates an exemplary algorithm for setting pacing parameters.

DETAILED DESCRIPTION

The present invention relates to a method or system for setting thepacing parameters and/or pacing configuration of a cardiac rhythmmanagement device for delivering resynchronization pacing to the leftventricle (LV) and/or the right ventricle (RV) in order to compensatefor ventricular conduction delays and improve the coordination ofventricular contractions. In accordance with the present invention,optimum pacing parameters may be computed based upon intrinsicconduction data derived from measurements of intra-cardiac conductiontimes using the sensing channels of an implanted device. Algorithms forcomputing and/or setting these pacing parameters may be implemented ineither the programming of an external programmer, in the programming ofthe implanted device itself, or as a manually implemented procedure(e.g., by using a printed table lookup to compute optimum parametersfrom intrinsic conduction data). In one embodiment, the externalprogrammer communicates with the implantable device over a telemetrylink and receives either raw electrogram data, markers corresponding toparticular sensed events, or measurements of the intervals betweenparticular sensed events as computed by the implantable device. Theexternal programmer may then compute optimal settings for pacingparameters which are either transmitted to the implantable device forimmediate reprogramming or presented to a clinician operating theexternal programmer as recommendations. Alternatively, the externalprogrammer may present the intrinsic conduction data to the clinicianwho then programs the implantable device in accordance with analgorithm. In another embodiment, the implantable device is programmedto automatically set certain pacing parameters in accordance withinformation gathered from its sensing channels.

As will be explained in more detail below, one aspect of the presentinvention involves the computation based upon intrinsic conduction dataof an optimum atrio-ventricular delay (AVD) interval for deliveringventricular resynchronization therapy in an atrial tracking and/oratrio-ventricular sequential pacing mode to patients having some degreeof AV block or having an atrial conduction delay. Another aspect relatesto the optimal pacing configuration for delivering ventricularresynchronization therapy to patients having a right ventricularconduction deficit.

1. Exemplary Hardware Platform

The following is a description of exemplary hardware components used forpracticing the present invention. A block diagram of an implantablecardiac rhythm management device or pulse generator having multiplesensing and pacing channels is shown in FIG. 1. Pacing of the heart withan implanted device involves excitatory electrical stimulation of theheart by the delivery of pacing pulses to an electrode in electricalcontact with the myocardium. The device is usually implantedsubcutaneously on the patient's chest, and is connected to electrodes byleads threaded through the vessels of the upper venous system into theheart. An electrode can be incorporated into a sensing channel thatgenerates an electrogram signal representing cardiac electrical activityat the electrode site and/or incorporated into a pacing channel fordelivering pacing pulses to the site.

The controller of the device in FIG. 1 is made up of a microprocessor 10communicating with a memory 12 via a bidirectional data bus, where thememory 12 typically comprises a ROM (read-only memory) and, or a RAM(random-access memory). The controller could be implemented by othertypes of logic circuitry (e.g., discrete components or programmablelogic arrays) using a state machine type of design, but amicroprocessor-based system is preferable. As used herein, theprogramming of a controller should be taken to refer to either discretelogic circuitry configured to perform particular functions or to thecode executed by a microprocessor. The controller is capable ofoperating the pacemaker in a number of programmed modes where aprogrammed mode defines how pacing pulses are output in response tosensed events and expiration of time intervals. A telemetry interface 80is provided for communicating with an external programmer 300. Theexternal programmer is a computerized device with an associated displayand input means that can interrogate the pacemaker and receive storeddata as well as directly adjust the operating parameters of thepacemaker. As described below, in certain embodiments of a system forsetting pacing parameters, the external programmer may be utilized forcomputing optimal pacing parameters from data received from theimplantable device over the telemetry link which can then be setautomatically or presented to a clinician in the form ofrecommendations.

The embodiment shown in FIG. 1 has four sensing/pacing channels, where apacing channel is made up of a pulse generator connected to an electrodewhile a sensing channel is made up of the sense amplifier connected toan electrode. A MOS switching network 70 controlled by themicroprocessor is used to switch the electrodes from the input of asense amplifier to the output of a pulse generator. The switchingnetwork 70 also allows the sensing and pacing channels to be configuredby the controller with different combinations of the availableelectrodes. The channels may be configured as either atrial orventricular channels allowing the device to deliver conventionalventricular single-site pacing with or without atrial tracking,biventricular pacing, or multi-site pacing of a single chamber. In anexample configuration, a left atrial sensing/pacing channel includesring electrode 53 a and tip electrode 53 b of bipolar lead 53 c, senseamplifier 51, pulse generator 52, and a channel interface 50, and aright atrial sensing/pacing channel includes ring electrode 43 a and tipelectrode 43 b of bipolar lead 43 c, sense amplifier 41, pulse generator42, and a channel interface 40. A right ventricular sensing/pacingchannel includes ring electrode 23 a and tip electrode 23 b of bipolarlead 23 c, sense amplifier 21, pulse generator 22, and a channelinterface 20, and a left ventricular sensing/pacing channel includesring electrode 33 a and tip electrode 33 b of bipolar lead 33 c, senseamplifier 31, pulse generator 32, and a channel interface 30. Thechannel interfaces communicate bi-directionally with a port ofmicroprocessor 10 and include analog-to-digital converters fordigitizing sensing signal inputs from the sensing amplifiers, registersthat can be written to for adjusting the gain and threshold values ofthe sensing amplifiers, and registers for controlling the output ofpacing pulses and/or changing the pacing pulse amplitude. In thisembodiment, the device is equipped with bipolar leads that include twoelectrodes which are used for outputting a pacing pulse and/or sensingintrinsic activity. Other embodiments may employ unipolar leads withsingle electrodes for sensing and pacing. The switching network 70 mayconfigure a channel for unipolar sensing or pacing by referencing anelectrode of a unipolar or bipolar lead with the device housing or can60.

The controller 10 controls the overall operation of the device inaccordance with programmed instructions stored in memory. The controller10 interprets electrogram signals from the sensing channels and controlsthe delivery of paces in accordance with a pacing mode. An exertionlevel sensor 330 (e.g., an accelerometer, a minute ventilation sensor,or other sensor that measures a parameter related to metabolic demand)enables the controller to adapt the atrial and/or ventricular pacingrate in accordance with changes in the patient's physical activity,termed a rate-adaptive pacing mode. The sensing circuitry of the devicegenerates atrial and ventricular electrogram signals from the voltagessensed by the electrodes of a particular channel. An electrogram isanalogous to a surface EKG and indicates the time course and amplitudeof cardiac depolarization and repolarization that occurs during eitheran intrinsic or paced beat. When an electrogram signal in an atrial orventricular sensing channel exceeds a specified threshold, thecontroller detects an atrial or ventricular sense, respectively, whichpacing algorithms may employ to trigger or inhibit pacing.

2. Cardiac Resynchronization Pacing Therapy

Cardiac resynchronization therapy is most conveniently delivered inconjunction with a bradycardia pacing mode. Bradycardia pacing modesrefer to pacing algorithms used to pace the atria and/or ventricles in amanner that enforces a certain minimum heart rate. Because of the riskof inducing an arrhythmia with asynchronous pacing, most pacemakers fortreating bradycardia are programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse. Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity. In an inhibited demand mode,a pacing pulse is delivered to a heart chamber during a cardiac cycleonly after expiration of a defined escape interval during which nointrinsic beat by the chamber is detected. For example, a ventricularescape interval for pacing the ventricles can be defined betweenventricular events, referred to as the cardiac cycle (CC) interval withits inverse being the lower rate limit or LRL. The CC interval isrestarted with each ventricular sense or pace. In atrial tracking and AVsequential pacing modes, another ventricular escape interval is definedbetween atrial and ventricular events, referred to as theatrio-ventricular pacing delay interval or AVD, where a ventricularpacing pulse is delivered upon expiration of the atrio-ventricularpacing delay interval if no ventricular sense occurs before. In anatrial tracking mode, the atrio-ventricular pacing delay interval istriggered by an atrial sense and stopped by a ventricular sense or pace.An atrial escape interval can also be defined for pacing the atriaeither alone or in addition to pacing the ventricles. In an AVsequential pacing mode, the atrio-ventricular delay interval istriggered by an atrial pace and stopped by a ventricular sense or pace.Atrial tracking and AV sequential pacing are commonly combined so thatan AVD starts with either an atrial pace or sense. When used in CRT, theAVD may be the same or different in the cases of atrial tracking and AVsequential pacing.

As described above, cardiac resynchronization therapy is pacingstimulation applied to one or more heart chambers in a manner thatcompensates for conduction delays. Ventricular resynchronization pacingis useful in treating heart failure in patients with interventricular orintraventricular conduction defects because, although not directlyinotropic, resynchronization results in a more coordinated contractionof the ventricles with improved pumping efficiency and increased cardiacoutput. Ventricular resynchronization can be achieved in certainpatients by pacing at a single unconventional site, such as the leftventricle instead of the right ventricle in patients with leftventricular conduction defects. Resynchronization pacing may alsoinvolve biventricular pacing with the paces to right and left ventriclesdelivered either simultaneously or sequentially, with the intervalbetween the paces termed the biventricular offset (BVO) interval (alsosometimes referred to as the LV offset (LVO) interval or VV delay). Theoffset interval may be zero in order to pace both ventriclessimultaneously, or non-zero in order to pace the left and rightventricles sequentially. As the term is used herein, a negative BVOrefers to pacing the left ventricle before the right, while a positiveBVO refers to pacing the right ventricle first. In an examplebiventricular resynchronization pacing mode, right atrial paces andsenses trigger an AVD interval which upon expiration results in a paceto one of the ventricles and which is stopped by a right ventricularsense. The contralateral ventricular pace is delivered at the specifiedBVO interval with respect to expiration of the AVD interval.

Cardiac resynchronization therapy is most commonly applied in thetreatment of patients with heart failure due to left ventriculardysfunction which is either caused by or contributed to by leftventricular conduction abnormalities. In such patients, the leftventricle or parts of the left ventricle contract later than normalduring systole which thereby impairs pumping efficiency. In order toresynchronize ventricular contractions in such patients, pacing therapyis applied such that the left ventricle or a portion of the leftventricle is pre-excited relative to when it would become depolarized inan intrinsic contraction. Optimal pre-excitation of the left ventriclein a given patient may be obtained with biventricular pacing or withleft ventricular-only pacing. Although not as common, some patients havea right ventricular conduction deficit such as right bundle branch blockand require pre-excitation of the right ventricle in order achievesynchronization of their ventricular contractions.

3. Optimal Adjustment of Pre-excitation Timing Parameters

Once a particular resynchronization pacing configuration and mode isselected for a patient, pacing parameters affecting the manner andextent to which pre-excitation is applied must be specified. For optimumhemodynamic performance, it is desirable to deliver ventricular pacing,whether for resynchronization pacing or conventional bradycardia pacing,in an atrial tracking and/or AV sequential pacing mode in order tomaintain the function of the atria in pre-loading the ventricles(sometimes referred to atrio-ventricular synchrony). Since the objectiveof CRT is to improve a patient's cardiac pumping function, it istherefore normally delivered in an atrial-tracking and/or AV sequentialmode and requires specification of AVD and BVO intervals which, ideally,result in the ventricles being synchronized during systole after beingoptimally preloaded during atrial systole. That is, both optimalinterventricular synchrony and optimal atrio-ventricular synchrony areachieved. As the term is used herein for biventricular pacing, the AVDinterval refers to the interval between an atrial event (i.e., a pace orsense in one of the atria, usually the right atrium) and the firstventricular pace which pre-excites one of the ventricles. The AVDinterval may be the same or different depending upon whether it isinitiated by an atrial sense or pace (i.e., in atrial tracking and AVsequential pacing modes, respectively), The pacing instant for thenon-pre-excited ventricle is specified by the BVO interval so that it ispaced at an interval AVD+BVO after the atrial event. It should beappreciated that specifying AVD and BVO intervals is the same asspecifying a separate AVD interval for each ventricle, designated asAVDR for the right ventricle and AVDL for the left ventricle. Inpatients with intact and normally functioning AV conduction pathways,the non-pre-excited ventricle will be paced, if at all, close to thetime at which that ventricle is intrinsically activated in order toachieve optimal preloading. In patients with normal AV conduction, theoptimal AVD and BVO intervals are thus related to both the intrinsicatrio-ventricular interval and the amount of pre-excitation needed forone ventricle relative to the other (i.e., the extent of the ventricularconduction deficit).

In order to optimally specify the AVD and BVO parameters for aparticular patient, clinical hemodynamic testing may be performed afterimplantation where the parameters are varied as cardiac function isassessed. For example, a patient may be given resynchronizationstimulation while varying pre-excitation timing parameters in order todetermine the values of the parameters that result in maximum cardiacperformance, as determined by measuring a parameter reflective ofcardiac function such as maximum left ventricular pressure change(dP/dt), arterial pulse pressure, or measurements of cardiac output.Determining optimal pacing parameters for an individual patient byclinical hemodynamic testing, however, is difficult and costly. It wouldbe advantageous if such optimal pacing parameters could be determinedfrom measurements of intrinsic conduction parameters which reflect howexcitation is conducted within the patient's heart during intrinsicbeats. In the approach of the present invention, therefore, intrinsicconduction data is collected from a surface EKG or from the sensingchannels of the implantable cardiac resynchronization device and thenused to compute optimum values of resynchronization pacing parameters.

As noted above, the objective of CRT is to restore a normal ornear-normal conduction sequence to ventricular contractions by usingpacing pulses to compensate for ventricular conduction deficits. CRT ismost commonly used to treat left ventricular dysfunction brought aboutby parts of the left ventricle contracting later than normal during anintrinsic cardiac cycle. Biventricular (or left ventricle-only) pacingaccomplishes this by pre-exciting the left ventricle with a first pacedelivered to the left ventricle followed by a pace to the rightventricle at the BVO interval (or intrinsic activation of the rightventricle in the case of left ventricle-only pacing). The left ventricleelectrode excites the left ventricular free wall, while the rightventricle electrode excites the ventricular septum. The desiredsituation is simultaneous contraction of the left ventricular free walland septum (septum-free wall fusion). When clinical hemodynamic testingis performed on a population of subjects with intact AV pathways todetermine the optimum values of the AVD and BVO intervals, there isfound to be a correlation between the optimum AVD and BVO intervals fora particular subject and that subject's measured conduction delaybetween the right and left ventricles during an intrinsic beat. Theoptimum AVD interval and the intrinsic atrio-ventricular interval arealso correlated from patient to patient. Therefore, the optimum AVD andBVO intervals for a particular patient may be estimated from intrinsicconduction data in terms of specified coefficients k_(n) as:BVO=k ₁·Δ_(RL) +k ₂andAVD=k ₃ AV _(R) +k ₃·Δ_(RL) +k ₄where Δ_(RL) is a measurement reflective of the interventricularconduction delay between the right and left ventricles such as theinterval between right left and ventricular senses or the QRS width on asurface ECG, and AV_(R) is the right intrinsic atrio-ventricularinterval measured as the interval between an atrial sense (or pace) anda right ventricular sense. It should be appreciated that these equationscan also be expressed in terms of separate AVD intervals for the rightand left ventricles, designated as AVDR and AVDL, respectively, andseparate measured intrinsic atrio-ventricular intervals for the rightand left ventricles, designated AV_(R) and AV_(L), respectively. Theintervals are thus related as:AV _(R) −AV _(L)=Δ_(RL)(if determined by right and left ventricularsenses)andAVDL−AVDR=BVOThe equations for computing optimal values of AVDR and AVDL are thus:AVDR=k ₅ AV _(R) +k ₆ AV _(L) +k ₇andAVDL=k ₈ AV _(R) +k ₉ AV _(L) +k ₁₀In certain implementations of the techniques described herein, separateintrinsic atrio-ventricular intervals are measured following an atrialsense and following an atrial pace which are then used to compute AVdelay intervals for pacing in atrial tracking and AV sequential modes,respectively. Also, unless otherwise specified, the term biventricularpacing should be taken to include left ventricle-only pacing. If thecomputed optimal BVO interval is a large negative value which is longerthan the right intrinsic atrio-ventricular interval, the right ventriclewill be activated intrinsically anyway so that the biventricular pacingis effectively left ventricle-only pacing.

In order to pre-derive the specified coefficients for later programminginto the system or for use by a clinician, clinical population data isobtained that relates particular values of the measured intrinsicconduction parameters to an optimum value of the pre-excitation timingparameter as determined by concurrent measurement of another parameterreflective of cardiac function (e.g., maximum dP/dt or minimum atrialrate). A linear regression analysis is then performed to derive valuesof the specified coefficients used in the formula for setting thepre-excitation timing parameter, the specified coefficients thus beingregression coefficients.

The techniques for setting resynchronization pacing parameters asdescribed above, as well as others to be described below, may beimplemented in a number of different ways. In one implementation, asystem for setting the pacing parameters includes an externalprogrammer. In an example embodiment, one or more intrinsic conductionparameters, as measured from electrogram signals generated by thesensing channels of an implantable cardiac resynchronization deviceduring intrinsic beats, are transmitted to the external programmer via awireless telemetry link. The measured intrinsic conduction parametersmay represent averages of values obtained during a specified number ofintrinsic beats. The external programmer then computes a pre-excitationtiming parameter such as the AVD or BVO in accordance with a formulathat equates an optimum value of the pre-excitation timing parameter toa linear sum of the measured intrinsic conduction parameters multipliedby specified coefficients. In an automated system, the externalprogrammer then automatically programs the implantable device with thecomputed optimum parameter values, while in a semi-automated system theexternal programmer presents the computed optimum values to a clinicianin the form of a recommendation. An automated system may also be made upof the implantable device alone which collects intrinsic conductiondata, computes the optimum parameter values, and then sets theparameters accordingly. In another embodiment, which may be referred toas a manual system, the external programmer presents the collectedintrinsic conduction data to a clinician who then programs theimplantable device with parameters computed from the intrinsicconduction data by, for example, using a printed lookup table andprocedure. Unless otherwise specified, references to a system forcomputing or setting pacing parameters throughout this document shouldbe taken to include any of the automated, semi-automated, or manualsystems just described.

4. Computation of Optimal Pacing Parameters Based Upon Atrial ConductionDelay

The above-described methods for computing optimal resynchronizationpacing parameters from intrinsic conduction data are based upon measuredintrinsic conduction data which include intrinsic atrio-ventricularintervals and/or interventricular conduction delays. Another measurableintrinsic conduction value which may be used in computing optimal pacingparameters is the conduction delay between the right and left atriaduring an intrinsic beat. One use of this technique is to computeoptimal resynchronization pacing parameters for patients with AV block.AV block refers to an impairment in the AV conduction pathways such thateither no intrinsic conduction from the atria to the ventricles occurs(complete or 3^(rd) degree AV block) or the intrinsic atrio-ventricularinterval is longer than normal. In patients with some degree of AVblock, the above techniques cannot be used to estimate the optimum AVDinterval for CRT because either no measured intrinsic atrio-ventricularinterval can be obtained or, if it can, it does not reflect optimumhemodynamics. In one aspect of the present invention, an optimum AVDinterval for pre-exciting the left ventricle in such patients mayinstead be computed from a linear function of the intrinsic delaybetween right atrial and left atrial activation, referred to as theRA-LA interval:AVD=k ₁₁(RA-LA)+k ₁₂where the AVD interval in this situation is the interval from an atrialevent to a left ventricular pace. The coefficients of the equation maybe obtained as before from a regression analysis of clinical populationdata. The technique may be implemented with the device in FIG. 1 usingthe right and left atrial sensing channels to measure the RA-LA intervalas the interval between right atrial pace or sense and a left atrialsense. After obtaining the optimum AVD interval, the BVO interval may beset to either a nominal value or computed from intrinsic conduction dataas described above.

The rationale for employing the RA-LA interval to compute an optimum AVDis as follows. When intrinsic depolarization is absent,intra-ventricular synchrony is optimized by delivering biventricularstimulation with or without an offset to result in septum-free wallfusion. Atrial-ventricular synchrony for the left atrium and leftventricle in this situation is optimized when the onset of leftventricular pressure rise coincides with the peak of left atrialcontraction. To achieve optimal atrio-ventricular synchrony in thetreatment of left ventricular dysfunction, stimulation to the leftventricle should therefore be applied at a certain time ahead of peakcontraction in the left atrium. FIG. 2 is a timing diagram whichillustrates this point. During an intrinsic beat, a right atrial senseRA_(S) is followed by a left ventricular sense LA_(S) which is thenfollowed by the peak of left atrial contraction X. In a subsequent beatwhere the left ventricle is paced at an optimal AVD interval withrespect to a right atrial sense, the left ventricular pace LV_(P)results in the onset of left ventricular pressure rise Y coinciding withthe peak of left atrial contraction X. The optimum AVD interval is thusproportional to the interval between the right atrial sense RA_(S) andthe peak of left atrial contraction X or its surrogate, the RA-LAinterval between the right atrial sense RA_(S) and the left atrial senseLA_(S).

The RA-LA interval may also be used to compute optimal resynchronizationparameters in patients with normal AV conduction. For example, if it isdetermined that intrinsic left ventricular activation occurs later thanleft atrial activation by a specified threshold amount, it may bedesirable to compute the resynchronization pacing parameters based uponthe intrinsic atrio-ventricular interval, the interventricularconduction delay, and the RA-LA interval. Thus, the right ventricle maybe paced at an AVDR interval computed as described above as:AVDR=k ₅ AV _(R) +k ₆ AV _(L) +k ₇orAVDR=k ₃ AV _(R) +k ₃·Δ_(RL) +k ₄The AVDL interval for pacing the left ventricle (or the BVO interval)may then be computed as a function of the RA-LA interval:AVDL=k ₁₃(RA-LA)+k ₁₄5. CRT Pacing Configuration and Mode for Patients with Atrial ConductionDeficit

In certain patients, an atrial conduction deficit exists such that leftatrio-ventricular synchrony does not occur during intrinsic beats evenif the intrinsic atrio-ventricular interval as measured from a rightatrial sense to a right ventricular sense is normal. Another aspect ofthe present invention involves determining if such an atrial conductiondeficit exists and adjusting pacing parameters accordingly. It may beimplemented in an implantable device for delivering CRT such asillustrated in FIG. 1 which has sensing/pacing channels for both atriaand both ventricles. In this embodiment, the implantable device isconfigured to deliver biventricular pacing in a manner specified byseparate AVDR and AVDL intervals, where the AVDR interval is the delaybetween a right atrial event and a right ventricular pace and the AVDLinterval is the delay between a right atrial event and a leftventricular pace. (The AVDR and AVDL parameters could, of course, bealternatively expressed in terms of an AVDR interval and a BVO intervalas above.) An additional pacing parameter is also provided for pacingthe left atrium, if necessary, referred to as the AAL interval which isan escape interval triggered by a right atrial event and results in aleft atrial pace upon expiration. In order to optimally set the pacingmode and pacing parameters, the relative times of left atrial and leftventricular activation during an intrinsic beat are first determined. Ifthe left atrium is depolarized later than the left ventricle by aspecified threshold amount, or if the measured RA-LA interval is above aspecified threshold amount, it can be surmised that a conduction deficitexists between the right and left atria. The device can therefore beconfigured to pace the left and right ventricles at AVDL and AVDRintervals calculated as described above from intrinsic conduction data(i.e., as a linear function of intrinsic AVD and Δ_(RL) intervals orintrinsic AV_(R) and AV_(L) intervals) and further configured to pacethe left atrium at an AAL interval which is shorter than the AVDLinterval by a specified offset.

6. Exemplary Algorithm for Computing Pacing Parameters and SettingPacing Configuration

FIG. 3 illustrates an exemplary algorithm which combines some of thetechniques described above which may be used for a device capable ofsensing/pacing both atria and both ventricles. At step S1, intrinsicconduction data is collected which reflect the intrinsic activationtimes of the four cardiac chambers. It is then determined at step S2whether the left ventricle is depolarized earlier than the left atriumby a specified threshold Th1. If so, then a pacing configuration isselected at step S3 such that the right and left ventricles arestimulated and the left atrium is also stimulated. At step S4, the AVDRand AVDL delays are calculated from intrinsic atrio-ventricular andinterventricular delay intervals, and the LA is stimulated with an AALdelay calculated as a function of the AVDL interval (e.g., such that AALequals the AVDL delay plus/minus a variable offset). If the result atstep S2 is negative, the algorithm proceeds to step S5 where it isdetermined whether or not the left ventricle is depolarized later thanthe left atrium by another threshold Th2. If so, then a pacingconfiguration is selected at step S6 in which only the left and rightventricles are paced. At step S7, the AVDL delay for pacing the leftventricle is calculated as a linear function of the RA-LA interval, andthe AVDR interval for pacing the right ventricle is calculated from theintrinsic atrio-ventricular interval. If the result at step S5 isnegative, a biventricular pacing configuration with no pacing of theleft atrium is selected at step S8, and the AVDR and AVDL intervals arecomputed from the intrinsic atrio-ventricular and interventricular delayintervals at step S9.

7. Pacing Configuration for Pre-excitation of the Right Ventricle

Another aspect of the present invention relates to providing cardiacresynchronization therapy for right bundle branch block (RBBB) patientswith or without LV dysfunction. Specifically, it relates to a pacingconfiguration and pacing parameter settings for improving RV hemodynamicfunction without compromising LV hemodynamic function. Currently, mostCRT devices are mainly designed for treating HF patients with LBBB orother conduction disorders affecting the left ventricle, their aim beingto improve LV hemodynamic function only. To achieve this goal, theelectrode for pacing (and possibly sensing) the left ventricle is placedin proximity to left ventricular free wall, and the right ventricularelectrode is placed in the right ventricle apex or in proximity to theventricular septum. The two electrodes can then provide synchronousstimulation at both sides of the left ventricular chamber by, forexample, simultaneously pacing the two sites or pre-exciting the leftventricular free wall. Research data have shown, however, that applyingCRT with such a pacing configuration in RBBB patients, where the rightventricle is pre-excited relative to the left, can impair leftventricular hemodynamic function. One way that this effect may bepartially ameliorated is by using a very long AVD interval to stimulatethe right ventricle, but this approach still does not eliminate thedeterioration of left ventricular hemodynamic function and, furthermore,does not provide optimal therapy to improve right ventricularhemodynamic function. A different placement for the right ventricularelectrode (farther away from the left ventricle) with appropriatelytimed stimulation is proposed which improves right ventricular functionwith little or no impact on normal left ventricular hemodynamicfunction.

In accordance with the invention, cardiac resynchronization therapy isprovided to a patient with a right ventricular conduction deficit with afirst electrode disposed near the right ventricular free wall and asecond electrode disposed near a cardiac site which is activated earlierthan the right ventricular free wall during an intrinsic beat. Thesecond electrode may be disposed, for example, in the right ventricularapex, near the right ventricular septum, or near the left ventricularfree wall. In one embodiment, the right ventricular free wall is pacedthrough the first electrode with a pacing mode such that a pacing pulseto the first electrode is triggered by a sense from the secondelectrode. In another embodiment, a third electrode is disposed in anatrium and an intrinsic atrio-ventricular interval AVI is measured froman atrial sense at the third electrode to a sense at the secondelectrode. The right ventricular free wall is then paced through thefirst electrode with an atrial tracking or AV sequential pacing modesuch that a pacing pulse to the first electrode is delivered followingan atrial event at an AV delay interval AVD, where the interval AVD isshorter than the measured atrio-ventricular interval AVI. In order tocompute the AVD interval, this embodiment may further include deliveringa pacing pulse to the first electrode, measuring a delay time D from thepacing pulse at the first electrode to a sense at the second electrode,and setting the AV delay interval AVD to be shorter than the measuredatrio-ventricular interval AVI by the delay time D, i.e.,AVD=AVI−D.The pace to the first electrode should be delivered at an intervalfollowing an atrial event selected to be shorter than the intrinsicatrio-ventricular interval to the first electrode following an atrialevent so that no intrinsic activation occurs.

In an example implementation, a first electrode is placed near the rightventricular free wall (preferably near the latest activated site), and asecond electrode is placed in the right ventricular apex. The intrinsicatrio-ventricular interval from an atrial sense to a right ventricularsense at the apex is measured, designated as AVI. Next, the rightventricular free wall is stimulated at a very short AV delay intervalAVD, and an interval D from the right ventricular pacing spike at thefree wall to a right ventricular sense at the apex is measured.Resynchronization therapy is then provided by pacing the rightventricular free wall in an atrial tracking and/or AV sequential pacingmode with an AVD interval shorter than the measured intrinsicatrio-ventricular interval AVI by the measured interval D. That is,AVD=AVI−D.In this manner, the right ventricular free wall is pre-excited so as tocompensate for the RBBB and produce a synchronized right ventricularcontraction without affecting normal left ventricular function.

In another example, a first electrode is placed near the rightventricular free wall, and a second electrode is placed near the rightventricular septum. The right ventricular free wall is then stimulatedupon sensing at the right ventricular septum (in VVI mode), or with anAVD interval which is slightly less than the intrinsic AV intervalbetween an atrial sense and a right ventricular sense at the septum (inVDD mode).

In another example, a first electrode is placed in the right ventricularfree wall, and a second electrode is placed near the left ventricularfree wall. The right ventricular free wall is stimulated upon sensing atthe left ventricular free wall (in VVI mode), or with an AVD intervalwhich is slightly less than the intrinsic AV interval between an atrialsense and the sense at the left ventricular free wall.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Other such alternatives, variations, and modifications are intended tofall within the scope of the following appended claims.

1. A method for setting optimal pacing parameters for delivering cardiacresynchronization therapy to a patient, comprising: measuring theinterval from a right atrial sense or pace to a left atrial sense in thepatient, designated as the RA-LA interval; setting an AVD interval fordelivering a ventricular pace following an atrial event in an atrialtracking or AV sequential pacing mode to an optimal value computed as alinear function of the measured RA-LA interval.
 2. The method of claim 1wherein the optimal value of the AVD interval is computed as:AVD=k ₁₁(RA-LA)+k ₁₂ where the coefficients k₁₁ and k₁₂ defining therelationship between the optimum AVD interval and the measured RA-LAinterval are derived from a linear regression analysis of clinicalpopulation data relating measured RA-LA intervals to an optimum AVDinterval for delivering cardiac resynchronization therapy as determinedby measurement of a cardiac function parameter.
 3. A method forproviding cardiac resynchronization therapy to a patient with a rightventricular conduction deficit, comprising: disposing a first electrodenear the right ventricular free wall; disposing a second electrode inthe right ventricular apex near a ventricular site which is activatedearlier than the right ventricular free wall during an intrinsic beat;pacing the right ventricular free wall through the first electrode witha pacing mode such that a pacing pulse to the first electrode istriggered by a sense from the second electrode.
 4. A method forproviding cardiac resynchronization therapy to a patient with a rightventricular conduction deficit, comprising: disposing a first electrodenear the right ventricular free wall; disposing a second electrode neara ventricular site which is activated earlier than the right ventricularfree wall during an intrinsic beat; disposing a third electrode in anatrium; measuring an intrinsic atrio-ventricular interval AVI from anatrial sense at the third electrode to a sense at the second electrodepacing the right ventricular free wall through the first electrode withan atrial tracking or AV sequential pacing mode such that a pacing pulseto the first electrode is delivered following an atrial event at an AVdelay interval AVD, where the interval AVD is shorter than the measuredatrio-ventricular interval AVI.
 5. The method of claim 4 wherein thesecond electrode is disposed in the right ventricular apex.
 6. Themethod of claim 4 wherein the second electrode is disposed near theright ventricular septum.
 7. The method of claim 4 wherein the secondelectrode is disposed near the left ventricular free wall.
 8. The methodof claim 4 further comprising: delivering a pacing pulse to the firstelectrode; measuring a delay time D from the pacing pulse at the firstelectrode to a sense at the second electrode; and, setting the AV delayinterval AVD to be shorter than the measured atrio-ventricular intervalAVI by the delay time D, i.e.,AVD=AVI−D.
 9. The method of claim 8 wherein the pace to the firstelectrode is delivered at an interval following an atrial event selectedto be shorter than the intrinsic atrio-ventricular interval to the firstelectrode following an atrial event so that no intrinsic activationoccurs.